There is accumulating evidence suggesting that tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)-receptor (R) 2 is a promising molecular target for cancer therapy. Therefore, we investigated the effect of chemotherapeutic agents on TRAIL-R2-mediated apoptosis and cytotoxicity in various human solid cancer cells. Treatment of the ACHN human renal cell carcinoma (RCC) cell line with agonistic TRAIL-R2 antibody (lexatumumab) in combination with 5-fluorouracil, vinblastine, paclitaxel, or docetaxel did not overcome resistance to these agents. However, treatment with lexatumumab in combination with doxorubicin had a synergistic cytotoxicity. Synergy was also achieved in two other human RCC cell lines, Caki-1 and Caki-2, and in eight primary RCC cell cultures. Sequential treatment with doxorubicin followed by lexatumumab induced significantly more cytotoxicity than reverse treatment or simultaneous treatment. Low concentrations of doxorubicin (0.1 and 1 µ µ µ µg/mL) significantly increased TRAIL-R2 expression at both the mRNA and protein levels. T umor necrosis factor-related apoptosis-inducing ligand (TRAIL) is potentially an effective anticancer agent because it selectively induces apoptosis in a variety of tumor cells, yet it is relatively non-toxic to normal cells.(1,2) TRAIL triggers apoptosis by binding to two receptors: TRAIL-receptor (R) 1 and TRAIL-R2. Activation of these receptors results in a signal transduction cascade that initiates intrinsic and extrinsic apoptotic pathways. (4) In addition, TRAIL binds to two other receptors, TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2), which lack a functional cytoplasmic death domain, and to the secreted tumor necrosis factor receptor homolog osteoprotegerin.(3,5) These receptors have been proposed to inhibit TRAIL-induced apoptosis. Potentially, the degree of TRAIL-R1-and TRAIL-R2-mediated apoptosis induced by TRAIL might be lowered in the presence of DcR1 and DcR2 activation. Therefore, using a specific activator of TRAIL-R1 or TRAIL-R2 is preferable to exclude interference from competition with DcR.It was reported that mouse or rabbit monoclonal antibodies (mAb) to human TRAIL-R1 or TRAIL-R2 have antitumor activities in vitro and in vivo.(6,7) These agonistic antibodies work by activating TRAIL-mediated apoptotic pathways in a manner similar to TRAIL, as agonistic TRAIL-R1 antibody induces poly(adenosine diphosphate-ribose) polymerase cleavage and the agonistic TRAIL-R2 antibody induces activation of caspases and c-Jun N-terminal kinase and p38 in tumor cells. (8) It has also been reported that mapatumumab, a fully human agonistic mAb specific for TRAIL-R1, reduces the viability of multiple types of tumor cells in vitro and inhibits tumor growth in vivo.(9) We recently reported that lexatumumab, a human agonistic TRAIL-R2 mAb, induces apoptotic cell death in renal cell carcinoma (RCC) cells. However, it requires cross-linking with IgG:Fc to exert apoptotic activity as a single agent.(10) Developing ways to optimize the effects of lexatumumab, particularly throu...

Objective: To evaluate the stone hardness in predicting the need for single or two sessions of retrograde intrarenal surgery (RIRS) for renal pelvis stones of 2-3 cm in size. Material and methods:Ninety-six patients (64 male and 32 female) with only renal stones (2.5±0.3 cm) underwent RIRS using flexible 7.5 Fr ureteroscope (FURS). The stone hardness was evaluated by preoperative non-contrast computed tomography (NCCT). The patients were divided into two groups based on stone hardness: Group I (n=54) (hard stones -Hounsfield Unit (HU) >1000) and group II (n=42) (not hard stone -HU <1000). The stone-free rate, the operative time, any intra or postoperative complications and the need for second sessions of RIRS were evaluated.Results: All stones were successfully accessed. Intraoperative complications were not reported. The initial stone-free rate was 40% in Group I and 95% in Group II after a single session (p= 0.01). A second session FURS was needed in 32 cases of Group I (40%) where postoperative CT showed significant residual stone fragments of 6±2 mm, and stone-free rate up to 100 percent. On the contrary only 2 cases from Group II underwent second session FURS (p= 0.01). The operative times were 75±15 minutes in Group I and 55±13 minutes in Group II (p<0.01). Six patients (4 in group I and 2 in group II) had postoperative high-grade fever (Clavien Grade II). Conclusion:Stone hardness had a significant impact on the decision of performing single versus two sessions of FURS for renal pelvic stones of 2-3 cm rather than the stone size alone.

About 4.6-16.2% of male adolescents may be affected by varicocele. The most important damaging effect of varicocele in adolescents is testicular growth arrest (hypotrophy). Ultrasound is more accurate compared with orchidometry in detecting hypotrophy. Histopathologically, the testis of adolescent boys affected by varicocele shows Leydig cell hyperplasia, decreased number of spermatogonia per tubule, spermatogenesis arrest, and sloughing of the germinal epithelium. Varicocele in adolescents negatively affects sperm density and motility, and this seems to be related to testicular volume. To treat or not to treat adolescent varicocele is a controversial question. This is due to conflicting reports about the effectiveness of varicocelectomy. On one hand, some studies demonstrated a significant catch-up growth of the testis but found that prophylactic varicocele repair might expose many individuals to the unnecessary risks of surgery. Furthermore, this catch up of testicular volume could be due to edema secondary to severing of lymphatics during the procedure. On the other hand, other studies found that varicocele correction in adolescents not only improved testicular hypotrophy but also improved semen quality. Complications of varicocelectomy, such as recurrence or hydrocele incidence, are less common in open varicocelectomy than in laparoscopic or percutaneous embolization when treating varicocele in adolescents.